Protein carboxyl methylase (PCM) is a ubiquitous soluble enzyme which reversibly carboxylates glutamic acid residues of many acidic proteins. Calmodulin is a protein which regulates the activity of a number of Ca ions-requiring enzymes in brain and elsewhere, and is an excellent substrate for PCM. When calmodulin is methylated, its ability to enhance the activity of phosphodiesterase is inhibited. The acetylcholine receptor is a complex of 5 polypeptides and is also an excellent substrate for PCM. Certain acidic phospholipids will inhibit PCM activity, implying that PCM may be regulated by cell membrane constituents.